2B. Elucidating role of BAP1 in fibrolamellar carcinoma

Fibrolamellar carcinoma (FLC) is a rare but deadly liver cancer, mostly occurring in young and otherwise healthy children or young adults. The scarcity of model systems to study the development of FLC has hampered the identification of effective therapies. Mutations in the BAP1 gene are associated with FLC, but mechanistic understanding how loss of BAP1 contributes to FLC tumorigenesis is unclear.

Our recent work shows that BAP1 may influence cellular identity in the liver. In this current project, we aim to obtain better mechanistic understanding of how loss of BAP1 in different liver cell types can influence cell identity and how this is linked to cancer development. We will use tissue-derived organoid cultures as well as pluripotent stem cell-based approaches combined with state-of-the-art CRISPR techniques to dissect the role of BAP1 in liver cell identity and liver development. Amongst others, techniques including immunofluorescence, RNA-sequencing, and epigenetic analyses will be pursued.

We will furthermore study the consequences of loss of BAP1 in mutated cells in the context of cellular crosstalk in cancer development. Thus, this project will contribute to a better understanding of FLC which may contribute to the development of novel FLC therapies.